Phylogenomics and antimicrobial resistance of Salmonella Typhi and Paratyphi A, B and C in England, 2016-2019

The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Salmonella Typhi and S. Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. S. Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of S. Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR S. Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for S. Typhi and S. Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR S. Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.